RETRACTED: Reduced interleukin-38 in non-small cell lung cancer is associated with tumour progression

Abstract

Lung cancer continues to be the leading cause of cancer-related deaths worldwide due to its high incidence, malignant behaviour and lack of major advancements in treatment strategy. The occurrence and development of lung cancer is closely related to inflammation. Thus, we conducted the present study to investigate the effects of IL-38 (interleukin-38), a newly identified anti-inflammatory factor, on non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancers. We first evaluated the IL-38 expression in 384 pairs of NSCLC samples and their adjacent normal mucosa by real-time PCR, ELISA (enzyme-linked immunoassay) and tissue microarrays. Then the role of IL-38 on patient survival rates, cancer progression and their sensitivity to chemotherapy drugs was assessed. IL-38 was barely expressed in the NSCLC tissues but highly expressed in the adjacent normal tissues. The downregulation of IL-38 was significantly correlated with the results of the American Joint Committee on Cancer stage and degree of differentiation, and it was also shown to be an independent prognostic indicator of disease-free survival and overall survival for patients with NSCLC. Overexpression of IL-38 in NSCLC cells suppressed cell migration, invasion, proliferation and colony formation through suppressing β-catenin. IL-38 inhibited NSCLC formation in a mice model and sensitized the cancer cells to chemotherapy drugs. Our results show that IL-38 plays an inhibitory role in NSCLC development and functions as a novel prognostic indicator and a potential therapeutic target.

IL-38: A New Player in Inflammatory Autoimmune Disorders

“…However, they also found that IL-6 production in human Mφs was significantly increased by full-length IL-38 (aa1–152) ranging from 0 to 20 ng/mL, especially at 20 and 10 ng/mL, stimulated by IL-1β or LPS, full-length IL-38 (10 ng/mL) was also capable of decreasing IL-6 and IL-8 levels when Mφs were exposed to ACM. In another study, Wang and colleagues [129] found that IL-38 suppresses the migration, invasion, and growth of non-small cell lung cancer cells in a dose-dependent manner at a concentration ranging from 0 to 100 ng/mL. Zhang and colleagues [59] reported that IL-38 suppresses VEGF-induced proliferation and migration of endothelial cells at a concentration of 1 or 5 ng/mL, and Yuan and colleagues [15] reported that IL-17, TNF-α, IL-1β, and MCP-1 mRNA levels were inhibited by IL-38 at concentrations of 20 ng/mL in THP-1 cells exposed to LPS.…”

IL-1 Family Members in Cancer; Two Sides to Every Story

“…In contrast, Wang et al demonstrated that IL-38 expression is decreased in NSCLC alone relative to adjacent non-tumor tissue (150), with lack of IL-38 expression correlating with poor prognosis. Administration of recombinant IL-38 inhibited β-catenin expression and reduced the proliferation, migration and invasion of lung cancer cells in vitro , while increasing cell death.…”

Transcription Factor p53 Suppresses Tumor Growth by Prompting Pyroptosis in Non-Small-Cell Lung Cancer

“…In contrast, there is much less information about the effects of pyroptosis. As a foreign composition in an organism, NSCLC cells predispose to initiate an autoimmune response and in turn trigger a series of inflammatory cascade [7]. Given these evidence, we thereby hypothesized that pyroptosis possesses a tight correlation with the progression of NSCLC.…”